Intraprostatic steroid hormones and endocrine disruptors in prostate cancer

evidence linking intraprostatic EDCs to prostate carcinogenesis is lacking.Notably, no studies have directly compared circulating and intraprostatic EDC levels within the same individuals to determine whether serum measurements accurately reflect tissue burden.In our preliminary work, we demonstrated detectable concentrations of EDCs in cancerous prostate tissue 15 , underscoring the biological plausibility of local retention.The purpose of this study was to comprehensively characterize intraprostatic steroid and EDC profiles within the tumor microenvironment, adjacent non-cancerous tissues from peripheral and transition zones, and plasma in patients with localized PCa that underwent robot-assisted radical prostatectomy.Furthermore, we evaluated the association between intratumoral steroid and EDC levels and tumor aggressiveness, as defined by ISUP Grade Group classification, as well as prognosis, assessed by prostate-specific antigen (PSA) levels six months after surgery, and risk categories.Finally, we explored the potential integration of steroid hormones and EDCs into machine learning models to enhance patient risk classification. Methods Study sample and study designThis prospective observational cohort included 178 consecutive patients with histologically confirmed localized PCa undergoing robot-assisted radical prostatectomy with 6-month follow-up (see Supplementary Methods).For each patient, three tissue specimens were collected intraoperatively: one tumor sample, one histologically non-malignant sample from the peripheral zone, and one histologically non-malignant sample from the transition zone of the prostate.Peripheral venous blood was collected at three predefined time points: on the day of surgery (baseline) and 3 and 6 months postoperatively.Three patients were excluded from the final analysis due to prior neoadjuvant hormonal therapy.Two additional patients were excluded due to alternative histopathological diagnoses (neuroendocrine carcinoma and intraductal carcinoma).All remaining patients had adenocarcinoma predominantly located in the peripheral zone of the prostate, with one case